This review examines the literature on drug interactions with omeprazole. Different mechanisms have been proposed as potential causes for such interactions. First, the absorption of some drugs might be altered due to the decreased intragastric acidity resulting from omeprazole treatment. There was no effect of omeprazole on the absorption of amoxycillin, bacampicillin and alcohol, while the amount of digoxin and nifedipine absorbed was increased by 10 and 21%, respectively, both increases probably being of no clinical significance. Secondly, the metabolism of high clearance drugs might be altered by changes in liver blood flow, although that is not affected by omeprazole, as indicated by the unchanged elimination of indocyanine green. In addition, the clearance of intravenously administered lidocaine (lignocaine) [a high clearance drug] was unaffected by omeprazole, further indicating that the latter does not alter liver blood flow. Thirdly, since omeprazole is a substituted benzimidazole, it might have the potential to interfere with the metabolism of other drugs by altering the activity of drug metabolising enzymes in the cytochrome P450 system, through either induction or inhibition. There is no indication of induction of this enzyme system in any interaction study with omeprazole. As regards inhibition, on the other hand, there is now considerable information available which indicates that omeprazole has the potential to partly inhibit the metabolism of drugs metabolised to a great extent by the cytochrome P450 enzyme subfamily IIC (diazepam, phenytoin), but not of those metabolised by subfamilies IA (caffeine, theophylline), IID (metoprolol, propranolol) and IIIA (cyclosporin, lidocaine, quinidine). Since relatively few drugs are metabolised mainly by IIC compared with IID and IIIA, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited.